Dimethyl fumarate refers to the dimethyl ester of fumaric acid. The compound has a molecular weight of 144.13 daltons and the following chemical structure:

This compound is also known by the names Dimethyl (E)-butenedioate (IUPAC), trans-1,2-Ethylenedicarboxylic acid dimethyl ester and (E)-2-Butenedioic acid dimethyl ester. The compound is also referred to by the acronym DMF. DMF can be synthesized according to the methods described in Chinese Patent Publication CN 101318901A, the disclosures of which are incorporated herein by reference. The compound in crystalline form has a disclosed melting point of between 102° C. and 105° C. Dimethyl fumarate is rapidly metabolized in vivo to monomethyl fumarate (MMF), and hence DMF is considered to be a prodrug of MMF.

Fumaderm®, an enteric coated tablet containing a mixture of salts of monoethyl fumarate and dimethyl fumarate, was approved in Germany in 1994 for the treatment of psoriasis. Fumaderm® is dosed three times per day with 1-2 grams/day administered for the treatment of psoriasis.
Tecfidera™, formerly called BG-12, is a delayed release (i.e., a capsule containing enteric-coated minitablets) oral dosage form of dimethyl fumarate. Tecfidera™ (dimethyl fumarate) was approved in the USA in 2013, and is dosed two times per day with 480 mg/day administered for the treatment of multiple sclerosis. Details concerning the clinical testing of BG-12 are disclosed in Sheikh et al., Safety Tolerability and Pharmacokinetics of BG-12 Administered with and without Aspirin, Key Findings from a Randomized, Double-blind, Placebo-controlled Trial in Healthy Volunteers, Poster PO4.136 presented at the 64th Annual Meeting of the American Academy of Neurology, Apr. 21-28, 2012, New Orleans, La.; Dawson et al., Bioequivalence of BG-12 (Dimethyl Fumarate) Administered as a Single 240 mg Capsule and Two 120 mg Capsules: Findings from a Randomized, Two-period Crossover Study, Poster P913 presented at the 28th Congress of the European Committee for Treatment and Research in Multiple Sclerosis, Oct. 10-13, 2012, Lyon, France; and Woodworth et al., Pharmacokinetics of Oral BG-12 Alone Compared with BG-12 and Interferon β-1a or Glatiramer Acetate Administered Together, Studied in Health Volunteers, Poster PO4.207 presented at the 62nd Annual Meeting of the American Academy of Neurology, Apr. 10-17, 2010, Toronto, Ontario, Canada.
Cocrystals are crystals that contain two or more non-identical molecules that form a crystalline structure. The intermolecular interactions between the non-identical molecules in the resulting crystal structures can result in physical and chemical properties that differ from the properties of the individual components. Such properties can include, for example, melting point, solubility, chemical stability, mechanical properties and others. Examples of cocrystals may be found in the Cambridge Structural Database and in Etter, et al., “The use of cocrystallization as a method of studying hydrogen bond preferences of 2-aminopyridine” J. Chem. Soc., Chem. Commun. (1990), 589-591; Etter, et al., “Graph-set analysis of hydrogen-bond patterns in organic crystals” Acta Crystallogr., Sect. B, Struct. Sci. (1990), B46: 256-262; and Etter, et al., “Hydrogen bond directed cocrystallization and molecular recognition properties of diarylgentisic acids” J. Am. Chem. Soc. (1990), 112: 8415-8426. Additional information relating to cocrystals can be found in: Carl Henrik Gorbotz and Hans-Petter Hersleth, “On the inclusion of solvent molecules in the crystal structures of organic compounds”; Acta Cryst. (2000), B56: 625-534; and Senthil Kumar, et al., “Molecular Complexes of Some Mono- and Dicarboxylic Acids with trans-1,4,-Dithiane-1,4-dioxide” American Chemical Society, Crystal Growth & Design (2002), 2(4): 313-318.